Generation of complex bone marrow organoids from human induced pluripotent stem cells.

The human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.

Transcriptomic responses of peripheral blood mononuclear cells to cyclosporin and etanercept in a female infant with juvenile generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. An early onset of the diseases is correlated with mutations among IL36RN, CARD14, AP1S3, MPO and SERPINA3 genes. Systemic biological agents including anti-TNF-α, anti-IL-17, anti-IL-12/IL-23, anti-IL1R, anti-IL1ß and anti-IL-36R act as novel treatment methods for GPP. Herein we report a female infant clinically diagnosed with GPP since she was 10-month-old. Results of whole-exome sequencing (WES) and Sanger sequencing revealed a reported heterozygous IL36RN (c.115+6T>C) and another reported heterozygous SERPINA3 frame-shifting variant (c.1247_1248del). Initial cyclosporin treatment for the patient led to a partial remission of the symptoms. However, the patient reached nearly total remission of pustules and erythema after anti-TNF-α inhibitor etanercept treatment. Results of further RNA sequencing (RNA-seq) done on peripheral blood mononuclear cells correlated with the clinical responses, showing that cyclosporin suppressed a portion of the neutrophil-related genes, while most genes associated with neutrophil activation, neutrophil-mediated immunity and degranulation were downregulated by the subsequent etanercept treatment. We report this case to demonstrate WES and RNA-seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.

Using EEG to investigate the influence of boredom on prospective memory in top-down and bottom-up processing mechanisms for intelligent interaction.

We aimed to investigate the alpha (α) activity in operators experiencing boredom while performing prolonged monitoring and prospective memory tasks using different processing mechanisms. Fifty-four participants underwent electroencephalography (EEG) and were found to have poorer prospective memory performance under top-down conditions. Further, α power and synchronisation were higher during bottom-up than in top-down processes, revealing an inhibition effect of the former. Significant differences in brain regions and hemispheres were identified to distinguish different cognitive processes in both information-processing mechanisms. Thus, people are likely to cope with boredom differently in terms of top-down and bottom-up processes. Specifically, a higher attention level was reported during top-down processing, to mitigate the negative influences of boredom. Overall, this study provides EEG evidence which suggests that prospective memory can be enhanced in top-down processing during prolonged monitoring tasks by increasing the salience of cues.

Boredom is a growing problem as tasks requiring monitoring increase. We explored how people process information to perform prospective memory tasks while monitoring. The prospective memory was poorer during top-down processing, but stronger cortical activation indicated an inhibitory effect on inattention. Information-processing mechanisms are suggested for designing boredom interventions.

Saliva-based COVID-19 detection: A rapid antigen test of SARS-CoV-2 nucleocapsid protein using an electrical-double-layer gated field-effect transistor-based biosensing system.

Facing the unstopped surges of COVID-19, an insufficient capacity of diagnostic testing jeopardizes the control of disease spread. Due to a centralized setting and a long turnaround, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), the gold standard of viral detection, has fallen short in timely reflecting the epidemic status quo during an urgent outbreak. As such, a rapid screening tool is necessitated to help contain the spread of COVID-19 amid the countries where the vaccine implementations have not been widely deployed. In this work, we propose a saliva-based COVID-19 antigen test using the electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET). The detection of SARS-CoV-2 nucleocapsid (N) protein is validated with limits of detection (LoDs) of 0.34 ng/mL (7.44 pM) and 0.14 ng/mL (2.96 pM) in 1× PBS and artificial saliva, respectively. The specificity is inspected with types of antigens, exhibiting low cross-reactivity among MERS-CoV, Influenza A virus, and Influenza B virus. This portable system is embedded with Bluetooth communication and user-friendly interfaces that are fully compatible with digital health, feasibly leading to an on-site turnaround, an effective management, and a proactive response taken by medical providers and frontline health workers.

Adjunctive dexmedetomidine infusion in open living donor hepatectomy: A way to enhance postoperative analgesia and recovery.

BACKGROUND: Open living donor hepatectomy (OLDH) is a highly painful procedure. Advanced strategies for enhancing perioperative analgesia and accelerating recovery are needed for patients undergoing OLDH. This study evaluated the effects of intravenous infusion of dexmedetomidine (DEX) during OLDH on postoperative analgesia and recovery. METHODS: This prospective, randomised, double-blinded, and placebo-controlled study included 34 patients randomised to a control group (group C) and a DEX group (group D). Utilisation of intravenous patient-controlled analgesia (IV-PCA) pump, pain intensity, and postoperative recovery variables were recorded. Moreover, intraoperative anaesthetic consumption, hemodynamic parameters, and fluid status were also recorded. RESULTS: During the first 24 hours after surgery, patients in group D had a lower pain intensity. The cumulative numbers of IV-PCA pump presses and fentanyl consumption within 24 and 48 hours postoperatively in group C were significantly higher than in group D. The time to first IV-PCA attempt was prolonged in group D. In addition, faster flatus passage was observed in group D. Intraoperatively, fewer anaesthetic agents were required in group D. Less fluctuation in hemodynamics and reduced bleeding were also found in group D. CONCLUSIONS: The present study revealed that the addition of intravenous infusion of DEX during OLDH provided several benefits in relieving postoperative pain and promoting recovery. Therefore, we concluded that intraoperative DEX infusion may play an important role in enhancing the recovery of patients undergoing OLDH.

The objective structured clinical examination as an assessment strategy for clinical competence in novice nursing practitioners in Taiwan.

BACKGROUND: The conventional written tests and professional assessment have limitation in fair judgement of clinical competence. Because the examiners may not have total objectivity and may lack standardization throughout the assessment process. We sought to design a valid method of competence assessment in medical and nursing specialties. This work was aimed to develop an Objective Structured Clinical Exam (OSCE) to evaluate novice nursing practitioners' clinical competency, work stress, professional confidence, and career satisfaction. METHODS: A Quasi-experimental study (pre-post). Fifty-five novice nursing practitioners received the OSCE three-months following their graduation, which consisted of four stations: history taking, physical examination, problem-directed management, interpersonal communication, and the required techniques of related procedures. The examiners had to complete an assessment checklist, and the participants had to complete a pre-post questionnaire (modified from a Nursing Competency Questionnaire, a Stress scale, and Satisfaction with Learning scale). RESULTS: Among the novice nursing practitioners, 41 of them (74.5 %) passed the exam with a mean score of 61.38 ± 8.34. There was a significantly higher passing rate among nurses who were working in medical-surgical wards (85.7 %) and the intensive care unit-emergency department (77.8 %) compared to novice nursing practitioners working in other units. All the novice nursing practitioners at Station A had poor performance in assessing patients with a fever. OSCE performance was more associated with educational attainment and work unit, rather than the gender. Finally, the participants showed statistically significant increases in their clinical competency, confidence in their professional competence, satisfaction with the clinical practice, and decreased work stress after the OSCE. CONCLUSIONS: We found that the OSCE process had a positive educational effect, in providing a meaningful and accurate assessment of the competence of novice nursing practitioners. An appropriate OSCE program is vital for novice nursing practitioners, educators, and administrators. The effective application of OSCEs can help novice nursing practitioners gain confidence in their clinical skills.

Do Congruent Auditory Stimuli Facilitate Visual Search in Dynamic Environments? An Experimental Study Based on Multisensory Interaction.

The purpose of this study was to investigate the cue congruency effect of auditory stimuli during visual search in dynamic environments. Twenty-eight participants were recruited to conduct a visual search experiment. The experiment applied auditory stimuli to understand whether they could facilitate visual search in different types of background. Additionally, target location and target orientation were manipulated to clarify their influences on visual search. Target location was related to horizontal visual search and target orientation was associated with visual search for an inverted target. The results regarding dynamic backgrounds reported that target-congruent auditory stimuli could speed up the visual search time. In addition, the cue congruency effect of auditory stimuli was critical for the center of the visual display but declined for the edge, indicating the inhibition of horizontal visual search behavior. Moreover, few improvements accompanying auditory stimuli were provided for the visual detection of non-inverted and inverted targets. The findings of this study suggested developing multisensory interaction with head-mounted displays, such as augmented reality glasses, in real life.

Alpha Oscillations in Parietal and Parietooccipital Explaining How Boredom Matters Prospective Memory.

Intelligent interaction alters previous human-machine task allocation patterns. Human workers will suffer from boredom and inattention, posing a significant challenge for the human-machine interaction loop. This study aims to investigate the relationship between boredom and prospective memory, which is a memory form including the detecting, identifying, and executing functions. Thus, the attention and memory mechanisms are critical to complete prospective memory tasks when bored. This study recruited twenty-eight participants and used electroencephalography to measure the alpha power in brain regions. The results indicated that parietal oscillations had a mediation effect on prospective memory, which could be associated with the frequent unstable attention. In addition, this study found that parietooccipital oscillations linked boredom and prospective memory, and the default mode network (DMN) and visual processing during boredom could better explain this finding. The findings of this study suggested that attention management and influences of processing visual information were starting points to cope with boredom because they could help prepare for prospective memory and make optimal decisions accordingly.

A Rapid Detection of COVID-19 Viral RNA in Human Saliva Using Electrical Double Layer-Gated Field-Effect Transistor-Based Biosensors.

In light of the swift outspread and considerable mortality, coronavirus disease 2019 (COVID-19) necessitates a rapid screening tool and a precise diagnosis. Saliva is considered as an alternative specimen to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the viral load is comparable to what are found in a throat and a nasal cavity. The electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) emerges as a promising candidate for salivary COVID-19 tests due to a high sensitivity, a portable configuration, a label-free operation, and a matrix insensitivity. In this work, the authors utilize EDL-gated BioFETs to detect complementary DNAs (cDNAs) and viral RNAs with various testing conditions such as switches of probes, temperature treatments, and matrices. The selectivity is confirmed with cDNA and noncomplementary DNA (ncDNA), exhibiting an eightfold difference in electrical signals. The matrix insensitivity is evaluated, and BioFETs successfully validate the detection of SARS-CoV-2 N-gene RNA down to 1 fm in diluted human saliva with a 95°C- and a 25°C-treatment, respectively. This proposed system has a high potential to be deployed for an on-site COVID-19 screening, improving the disease control and benefitting frontline healthcare system.

Prevalence of musculoskeletal discomfort among female cabin crew in Taiwan.

OBJECTIVES: This study investigated the prevalence of musculoskeletal discomfort among female cabin crew through cabin tasks and demographic factors, including age and seniority. METHODS: This study conducted an online questionnaire survey targeted at female cabin crew in Taiwan and ensured that the sample size was with a statistical power of 0.95. This study evaluated the work intensity by ranking six common cabin tasks and examined musculoskeletal discomfort with Cornell Musculoskeletal Discomfort Questionnaire. Descriptive statistics were used to learn the work intensity and discomfort conditions. In addition, the Chi-square test of independence and multivariate adjustment were applied to clarify the impact of age and occupation on musculoskeletal discomfort in the neck, shoulders, and lower back. RESULTS: This study enrolled 88 female cabin crew members. Handling carry-on baggage was voted as the highest intensity cabin task (40%), which was also ranked as the strongest intensity on shoulders. Meanwhile, the upper trunk was more prevalent in musculoskeletal discomfort. Moreover, after multivariate adjustment with controlling the effect of age, this study found a marginal significant association (p = .09) between seniority and right shoulder discomfort for younger staff. CONCLUSION: This study found that handling carry-on baggage was associated with musculoskeletal complaints in the shoulders. Therefore, this study suggested that shoulders, especially for the right side might be related to the occupational injury, which was prevalent along with seniority among the younger crew. Overall, this study provided the preliminary findings to improve occupational training for preventive health.

Abdominal obesity and hypertension are correlated with health-related quality of life in Taiwanese adults with metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MetS) gains more attention due to high prevalence of obesity, diabetes and hypertension among adults. Although obesity, diabetes and hypertension can certainly compromise health-related quality of life (HRQoL), the correlations of sociodemographic factors, quality of life and MetS remains unclear. This study aims to investigate the association between HRQoL and MetS in an Asian community of the sociodemographic characteristics. RESEARCH DESIGN AND METHODS: We performed a cross-sectional study by recruiting 2588 Taiwanese patients aged ≥30 years between August 2015 and August 2017. Sociodemographic data and anthropometric variables were obtained from medical records and physical examination. Meanwhile, HRQoL was assessed by 36-Item Short-Form Health Survey questionnaires. RESULTS: The overall prevalence of MetS was 32.8%. Multivariate analysis revealed that age ≥65 years (OR=1.987, p<0.001), body mass index (BMI) ≥24 kg/m2 (OR=7.958, p<0.001), low educational level (OR=1.429, p=0.014), bad self-perceived health status (OR=1.315, p=0.01), and betel nut usage (OR=1.457, p=0.048) were associated with the development of MetS. For patients with MetS, the physical and mental health domains of HRQoL are negatively correlated with abdominal obesity and hypertension, respectively. CONCLUSIONS: Adult MetS in Taiwan was associated with certain sociodemographic factors including older age, high BMI, low educational level, bad self-perceived health status, and betel nut use. Abdominal obesity and hypertension was correlated with HRQoL in patients with MetS.

Fentanyl-based intravenous patient-controlled analgesia with low dose of ketamine is not inferior to thoracic epidural analgesia for acute post-thoracotomy pain following video-assisted thoracic surgery: A randomized controlled study.

BACKGROUND: Thoracic epidural analgesia is the preferred method for postoperative analgesia following thoracic surgery. However, intravenous patient-controlled analgesia (IVPCA) may be an effective alternative. This study was conducted because few scientific reports exist comparing fentanyl-based IVPCA including a low dose of ketamine (fk-IVPCA) with thoracic patient-controlled epidural analgesia (t-PCEA) for the treatment of postoperative pain after video-assisted thoracic surgery (VATS). METHODS: This prospective, and randomized study included 70 patients randomized into fk-IVPCA and t-PCEA groups. Pain at rest and during movement, successful and unsuccessful triggers after pressing the PCA device button, the need for rescue analgesia, drug-related adverse events, and patient satisfaction were recorded for 48 hours postoperatively. RESULTS: No significant differences in the intensity of pain at rest or during movement were observed between the 2 groups within 48 hours postoperatively. The number of unsuccessful PCA triggers in the t-PCEA group 0 to 4 hours after surgery was significantly higher than that in the fk-IVPCA group. However, the numbers of successful PCA triggers in the fk-IVPCA group at 4 to 12 and 0 to 24 hours after surgery were significantly higher than those in the t-PCEA group. The incidence of analgesic-related side effects and patient satisfaction were similar in both groups. CONCLUSIONS: Compared with t-PCEA, the addition of a subanesthetic dose of ketamine to fentanyl-based IVPCA resulted in similar pain control after VATS with no increase in the incidence of drug-related adverse effects. The results confirm that both multimodal intravenous analgesia and epidural analgesia can provide sufficient pain control and are safe strategies for treating acute post-thoracotomy pain.

Correlates Between Health Beliefs and Health-Promoting Lifestyle Profiles in the Development of Metabolic Syndrome in Taiwan.

Differences in sociodemographic variables, health beliefs, and a healthy lifestyle all contribute to the varied prevalence of metabolic syndrome (MetS). We investigated the associations among MetS-related risk factors and performed a cross-sectional study, recruiting 1741 Taiwanese residents aged ≥30 years, between August 2014 and August 2015. Data were obtained on sociodemographic factors, health beliefs, and health-promoting lifestyle profiles using questionnaires. Multivariate analysis revealed that age ≥65 years (odds ratio [OR] = 2.17), low educational level (OR = 1.46), body mass index ≥24 kg/m2 (OR = 9.00), more health responsibility (OR = 1.08), and less exercise (OR = 0.924) were independent risk factors for MetS development. A correlation existed between health beliefs and health-promoting lifestyle profiles, suggesting that the establishment of an effective health-promoting program should consider participants' health beliefs.